This application is a new request for partial funding of a three channel 600 MHz NMR spectrometer, and conventional pulse gradient inverse triple resonance probe {1H, 13C, 15N} in the Pennsylvania State University College of Medicine (COM). This new instrument will compliment the recently ordered 500 MHz spectrometer for the COM campus and together provide state-of-the-art capabilities to a wide range of research groups here at the COM as well as several groups from the PSU main campus. The College of Medicine, the Departments of Biochemistry and Molecular Biology, Pharmacology, Cellular and Molecular Physiology, the Cancer Institute, and the PSU Huck Institute (Life Sciences Consortium) have 35% matching funds for these purchases. An additional institutional commitment is provide in the form of COM funds to purchase a 1H, 13C, {15N} inverse triple resonance TCI cryoprobe, 100% salary support for three years and 50% salary support thereafter for the recently hired NMR facility manager in the Department of Biochemistry and Molecular Biology and full funding of the operation of the instrument during its first year. The proposed 600 MHz NMR and ordered 500 MHz instruments will be located on the second floor of the main building (Crescent) which was deemed the best suited for these instruments based upon a site planning report from the Bruker OMNI service. In addition to the renovations need the NMR spectrometers additional renovations are planned in the surrounding modules that will allow the placement of a number of other shared instruments including several mass spectrometers, graphics workstations, and X-ray crystallographic facility. The COM has an excellent record in the administration and upkeep of shared instruments. The requested spectrometer will support the research efforts in the COM and at the PSU UP campus studying protein structure and dynamics for a range of medically relevant proteins and also several groups in the COM studying metabolic flux in human brain and muscle. The cryoprobe technology has been demonstrated to provide a significant improvement in signal-to-noise ratios for studies of biological relevant macromolecules and for metabolic flux analysis. This will allow researcher groups here and at the PSU main campus to perform technically demanding experiments such as studying the unfolded state structure of proteins, determining the structures of large proteins or protein complexes, and following metabolic flux using 13C-labeled metabolites. In addition, for many experiments the cryoprobe provides increased throughput that will accelerate the NIH supported research projects allowing and allow a larger group of researches access to this instrument. [unreadable] [unreadable]